This invention relates to a multistage combination preparation made up of 21 or 28 units, each to be administered on separate days, and its use for oral contraception for females of child bearing age.
Multistage combination preparations for oral contraception are known, for example, from DE-A No. 2,365,103 (U.S. Pat. No. 3,957,982) and the patents derived therefrom. Usually two or three stages are involved. These multistage preparations consist of 21 or 28 dragees, and contain, in the first stage, 4-6 dragees wherein each dragee contains an amount of estrogen corresponding to 0.02-0.05 mg of ethinylestradiol, and an amount of gestagen (progestogen) corresponding to 0.04-0.09 mg of d-norgestrel; in the second stage, (which can be a continuation of the first in essence), 4-6 dragees each containing onefold to twofold the amount of estrogen of the first stage, for example 0.03-0.05 mg of ethinylestradiol, and onefold to one and one-half-fold the amount of gestagen of the first stage, for example 0.05-0.125 mg of d-norgestrel; and, in the third stage, 9-11 dragees each containing an amount of estrogen that is larger than or exactly as large as that in the first stage and smaller than or exactly as large as in that in the second stage, for example, 0.025-0.050 mg of ethinylestradiol, and an amount of gestagen larger than that in the second stage, but no larger than three times as large as that in the first stage, for example 0.10-0.25 mg of d-norgestrel, and optionally, in the fourth stage, 7 dragees without estrogen and without gestagen. The number of dosage units in the three stages which contain estrogen and gestagen amounts to 21; to adapt to the 28-day cycle, 7 units free of active ingredient can be additionally included with the 21 units containing active agent.
Such multistage preparations provide higher compatibiltiy and improved cycle control as compared with the known combination preparations for cyclic or sequential usage.
European Patent Application No. 81200240 (publication No. 36229) describes a variant of a multistage preparation. This version is characterized in that the units of the first stage contain a higher amount of estrogen than the units of the subsequent stages.
In the multistage combination preparations, the estrogens can be utilized in amounts smaller than 0.05 mg of ethinylestradiol. Because of their staggered structures, the amounts of gestagen can likewise be kept at a low level. In this way, contraceptives are obtained using the lowest amounts of hormones thus practiced.
However, it is still desirable that the amount of gestagen be lowered still further.